The therapy of obstructive bronchopneumopathy with substances having antimuscarine activity, known in folk medicine by the name of "cigarette for asthma" and containing Datura stramonium, has been again recently studied under the modern form of the predosed aerosol. As a matter of fact, the vagal reflex bronchial obstruction in the pathogenesis of the obstructive diseases of the respiratory organs has a role much more important than that previously believed. A number of noxious factors abounding in industrial society (SO.sub.2, sufuric acid, ammonia, exhaust gas, cigarette smoke and others) reflexively causes an increase in the tone of the bronchial muscles, which can be prevented by antimuscarine agents. Thus at the present time antimuscarine agents, administered mainly by inhalation, are becoming the therapeutical agents of choice (anta-agonists, theophillinic, corticosteroids, disodium chromoglycate).
The present invention relates to novel anti-bronchospastic compounds to be administered by inhalation and which compose some quaternized derivatives of 10-(1-azobicyclo-[2.2.2.]-oct-3-yl-methyl)-10-H-phenothiazine (i.e. mequitazine).
Mequitazine is an anti-histamine drug, whose activity takes place through a histamine antagonism at the level of the H.sub.1 receptors and is consequently indicated for the symptomatic treatment of a number of allergic states (hay-cold, vasomotor rhinitis, nettle-rash, itch, allergic conjunctivities, Quincke oedema, allergic eczema, insect stings), in the same manner as classic anti-histaminic drugs, among which it is characterized according to published papers by a long lasting action and by a scarcity of side effects of the CNS level.
In only one paper (Med. et Hyg. 41, 7, 1983) is there a report of the protective action of mequitazine towards the bronchial hyperreactivity of patients affected by asthma, under well defined conditions.
Like effects have been previously claimed for other anti-histaminic drugs, such as promethazine, mepyramine, clopheniramine and clemastine, which however in the classic textbook of pharmacology (Goodman and Gilman, the Pharmacological Basis of Therapeutics, 627, McMillan N.Y. 1980) are defined as "singularly inefficacious in the bronchial asthma".
UK Patent specification No. 1250534 claims mequitazine and its analogues as possible antihistaminic, anti-depressant and psycholeptic agents for oral, parenteral and rectal administration. Some homologues of mequitazine, including their salts, are described in this patent and its scope is extended also to the related quaternary ammonium derivatives, none of which however is described under the chemical and/or pharmacological aspect.